| Dysregulated SASS6 expression promotes increased ciliogenesis and cell invasion phenotypes | | Dysregulated SASS6 expression promotes increased ciliogenesis and cell invasion phenotypes | Hargreaves E, Collinson R, Jenks AD, Staszewski A, Tsalikis A, Bodoque R, Arias-Garcia M, Abdi Y, Al-Malki A, Yuan Y, Natrajan R, Haider S, Iskratsch T, Wang WJ, Godinho S, Palaskas NJ, Calvo F, Vivanco I, Zech T, Tanos BE. | 2025-08-17T22:00:00Z | <p></p><h2>Abstract</h2><p>Centriole and/or cilium defects are characteristic of cancer cells and have been linked to cancer cell invasion. However, the mechanistic bases of this regulation remain incompletely understood. Spindle assembly abnormal protein 6 homolog (SAS-6) is essential for centriole biogenesis and cilium formation. SAS-6 levels decrease at the end of mitosis and G1, resulting from APCCdh1-targeted degradation. To examine the biological consequences of unrestrained SAS-6 expression, we used a nondegradable SAS-6 mutant (SAS-6ND). This led to an increase in ciliation and cell invasion and caused an up-regulation of the YAP/TAZ pathway. SAS-6ND expression resulted in cell morphology changes, nuclear deformation, and YAP translocation to the nucleus, resulting in increased TEAD-dependent transcription. SAS-6-mediated invasion was prevented by YAP down-regulation or by blocking ciliogenesis. Similarly, down-regulation of SAS-6 in DMS273, a highly invasive and highly ciliated lung cancer cell line that overexpresses SAS-6, completely blocked cell invasion and depleted YAP protein levels. Thus, our data provide evidence for a defined role of SAS-6 in cell invasion through the activation of the YAP/TAZ pathway.<br></p> | <p><a href="https://doi.org/10.26508/lsa.202402820" target="_blank">Life Sci Alliance. 2025 Aug 18;8(10):e202402820.</a><br></p> | 551 | | |
